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Biomedical subjects

D T Dieterich

Publications and source records attributed to D T Dieterich.

At least 19 recordsLinked to original sources
PubMed2006

Zidovudine use but not weight-based ribavirin dosing impacts anaemia during HCV treatment in HIV-infected persons.

Anaemia during peginterferon (PEG-IFN) and ribavirin (RBV) therapy is common in human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients despite the use of lower doses of RBV than are recommended for HIV-seronegative persons. In addition, concurrent zidovudine (ZDV) may exacerbate the anaemia caused by PEG-IFN and RBV. We retrospectively analysed the incidence of anaemia, RBV dose reduction and epoetin-alpha (EPO) use among coinfected patients treated with PEG-IFN and weight-based RBV (800-1400 mg/day) who enrolled in two clinical trials and had haemoglobin (Hb) levels assessed at baseline and after 4 and/or 12 weeks of HCV treatment. Overall, 217 patients were included; pre-treatment Hb levels (mean 14.7 g/dL) were similar in all patients, including ZDV users (29% of patients). After 4 weeks of therapy, the mean Hb decline was greater among ZDV recipients (3.13 g/dL) compared with those on other anti-retroviral treatment (ART) (2.13 g/dL) or on no ART (1.47 g/dL) (P < 0.0001). RBV dose reduction and EPO use were more common in patients taking ZDV compared with those not taking ZDV (P < 0.0001). RBV dose was not associated with Hb reduction, RBV dose reduction or EPO use. Virologic response after 12 weeks of therapy and the treatment discontinuation rate did not differ by ZDV use. The use of ZDV but not weight-based RBV dosing was associated with an increased risk of anaemia, RBV dose reduction or EPO use in coinfected patients treated with PEG-IFN/RBV. However, ZDV use was not associated with higher rates of treatment discontinuation or lower early virologic response rates. HIV and hepatitis C care providers should be cognizant of these data.

Adult↗
PubMed2001

Effect of HIV-1 infection on lymphocyte proliferation in gut-associated lymphoid tissue.

OBJECTIVE: To determine the change in the percentage of proliferative and activated lymphocytes in gut-associated lymphoid tissue (GALT) in HIV-1-infected subjects compared with that in uninfected controls. METHODS: We measured the percentage of proliferative (Ki-67+) and activated (CD-69+, HLA-DR+, CD45RO+) lymphocytes from GALT and peripheral blood in chronically HIV-1-infected (12) and uninfected (9) individuals. RESULTS: The percentage of proliferative GALT CD4+ T cells was increased in HIV-1-infected control subjects compared with that in uninfected controls (p <.007). Based on immunohistochemical staining, proliferative T cells were principally located in the parafollicular area surrounding lymphoid aggregates. The percentage of activated GALT lymphocytes, however, was not significantly different in HIV-1-infected individuals, whereas it was significantly increased in the peripheral blood of HIV-1-infected individuals. The percentage of peripheral blood lymphocytes trafficking to the intestine was also not significantly different in HIV-1-infected individuals compared with that in uninfected controls. CONCLUSIONS: CD4+ T cell proliferation in GALT is increased in HIV-1 infection without a significant alteration in the percentage of peripheral blood T cells trafficking to the gastrointestinal mucosa.

Adult↗
PubMed2001

The histopathology of 103 consecutive colonoscopy biopsies from 82 symptomatic patients with acquired immunodeficiency syndrome: original and look-back diagnoses.

OBJECTIVE: To compare the primary diagnoses assigned by general surgical pathologists on a series of 103 consecutive colon biopsies from individuals infected with human immunodeficiency virus (HIV) with diagnoses rendered by a pathologist with extensive experience in gastrointestinal pathology in HIV/acquired immunodeficiency syndrome. DESIGN: New sections were cut from paraffin blocks of 103 consecutive colon biopsies taken during colonoscopies of 82 different HIV-infected patients; all new sections were stained with hematoxylin-eosin. These individuals either had negative stool studies or had failed to respond to therapy and had chronic large bowel symptoms, such as frequent small volume-type diarrhea, tenesmus, and/or bright red blood per rectum. Immunohistochemistry for cytomegalovirus (CMV) was performed on 18 of 22 specimens originally diagnosed with CMV colitis. RESULTS: The initial study yielded 70 (68%) negative or nonspecific diagnoses, 22 (21%) cases of CMV colitis, 5 (5%) Cryptosporidium diagnoses, 2 cases each of adenomatous polyps and Kaposi sarcoma, and 1 case each of spirochetosis and squamous cell carcinoma of the anorectum. Review of the recuts yielded 64 (62%) negative or nonspecific diagnoses, 12 (12%) new adenovirus infections (3 combined with CMV), and 11 (11%) lone CMV infections. Three attaching and effacing bacterial infections were diagnosed, 1 with adenovirus coinfection. A total of 4 spirochetosis cases were found on review. Seven (7%) of the biopsies showed at least 1 coinfection. Nine biopsies had features suggestive of inflammatory bowel disease. CONCLUSIONS: Colonoscopy with biopsy after negative stool studies or failure to respond to therapy yielded a high proportion of negative or nonspecific diagnoses. Adenovirus and enteropathogenic bacterial infections had been totally overlooked on initial examination. It takes particular experience to evaluate gastrointestinal biopsies from HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Treatment of hepatitis C virus and HIV coinfection: the road less traveled.

The use of HAART for HIV infection has significantly reduced morbidity and mortality secondary to AIDS-related opportunistic infections. In hepatitis C virus (HCV)-HIV-coinfected patients, progression to AIDS, cirrhosis, and liver failure from HCV infection has become an important issue. Liver disease caused by chronic HCV infection has become the second leading cause of death in some HIV-infected populations. HIV infection is not a contraindication to HCV infection therapy. Several clinical studies have borne out that HCV infection can be safely and successfully treated in HIV-HCV-coinfected patients. These patients should be evaluated and offered anti-HCV treatment as clinically indicated.

Antiretroviral Therapy, Highly Active↗
PubMed2000

Hepatitis C virus/human immunodeficiency virus coinfection: clinical management issues.

The use of highly active antiretroviral therapy (HAART) has extended the healthy lifespan of patients infected with human immunodeficiency virus (HIV); deaths among people with AIDS declined for the first time in 1996, after the institution of this therapeutic approach. As the life expectancy of HIV-infected patients increases, greater attention will need to be focused on the recognition and management of potentially severe concurrent illnesses that may increase their mid- to long-range morbidity and mortality. The incidence of infection by hepatitis C virus (HCV) is increased among patients with HIV disease, reflecting shared epidemiological risks. HCV not only may have an impact on the health status of HIV-infected patients but also may decrease their quality of life and increase their health care costs. Although clinicians have been reluctant to treat viral hepatitis C in the HIV-infected population, this therapeutic nihilism is unwarranted. The majority of studies have concluded that treatment of hepatitis C in HIV-infected patients results in an initial efficacy and long-term response similar to those in the HIV-seronegative population. Furthermore, treatment of HCV infection in HCV/HIV-coinfected patients may improve tolerance for antiretroviral medications. Physicians caring for patients with HIV infection require up-to-date information to make rational decisions regarding HCV coinfection to ensure that morbidity and mortality are minimized and that quality of life and medical care costs are optimized.

Disease Management↗
PubMed2000

Infections of the liver in HIV-infected patients.

The liver is a common site of pathology in HIV-infected patients. In patients with controlled HIV and minimal immunosuppression, infection with hepatitis viruses is common owing to the risk factors of sexual transmission or parenteral drug use. In patients with AIDS, the liver is a common site of lymphohematogenous dissemination of several infectious pathogens. A thorough diagnostic approach leads to a diagnosis of most hepatobiliary processes. The therapeutic nihilism that has surrounded hepatic disease, including viral hepatitis, is unwarranted, because treatment of the underlying HIV and the hepatic process may improve the quality of life and longevity of these patients.

AIDS-Related Opportunistic Infections↗
PubMed1999

Hepatitis C virus and human immunodeficiency virus: clinical issues in coinfection.

The prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection ranges from nearly 30% to over 50%, depending on the population. Shared modes of transmission and the success of current antiretroviral regimens have contributed to the emergence of HCV as a significant pathogen in the HIV-positive population. HIV coinfection appears to worsen HCV infection, with studies showing more severe fibrosis, a higher frequency of cirrhosis, and increased deaths from liver disease. HIV coinfection may also increase the rate of maternal-fetal transmission of HCV. Similarly, studies suggest a more rapid progression to AIDS or death for HCV genotypes 1a and 1b than for other genotypes in HIV-infected patients with hemophilia. Highly active antiretroviral therapy (HAART), such as HIV protease inhibitors, has no effect on HCV infection and may transiently increase ALT, AST, and hepatitis C viral load. Hepatotoxicity associated with HAART may or may not be related to the presence of HCV and may depend on the specific agents used. Data suggest that treating chronic hepatitis C in HIV-co-infected patients can decrease fibrosis, increase T-cell responsiveness to HCV antigens, and decrease the rate of fatal hepatomas. Interferon alpha may provide sustained biochemical or virologic responses in HIV/HCV-coinfected patients. The combination of interferon-alpha and ribavirin may also be a treatment option but is more complex, and additional research is needed. Treating HCV infection in HIV/HCV-coinfected individuals may help lower the hepatitis C viral load and permit treatment with protease inhibitors.

Anti-HIV Agents↗
PubMed1999

Activity of combination therapy with interferon alfa-2b plus ribavirin in chronic hepatitis C patients co-infected with HIV.

The hepatitis C virus (HCV) and the human immunodeficiency virus (HIV) often co-infect the same individuals because they share comparable routes of transmission. Co-infection with HIV in those patients infected with HCV influences the accuracy of HCV diagnostic testing, levels of HCV viremia, severity of liver histopathology, and rate of progression to cirrhosis. By contrast, the effect of HCV co-infection on HIV disease is unclear. Nevertheless, the combination therapy containing recombinant interferon alfa-2b (rIFN-alpha 2b) plus ribavirin has been shown to be efficacious in the treatment of chronic hepatitis C, whereas alpha interferon monotherapy has been shown to be efficacious in patients co-infected with HCV and HIV. It is therefore logical to propose and test the hypothesis that combination rIFN-alpha 2b/ribavirin therapy will also benefit patients who are co-infected with HCV and HIV. A double-blind, placebo-controlled study is presently under way to investigate this hypothesis.

Antiviral Agents↗
PubMed1999

Hepatitis B and C in the context of HIV disease: implications for incarcerated populations.

HIV-infected inmates are often co-infected with hepatitis B and/or hepatitis C virus. To describe the burden of HIV in the incarcerated population today, one must consider the impact of co-infection. HIV may dramatically modify the course of viral hepatitis infection, especially chronic hepatitis C. The converse is uncertain: chronic hepatitis does not seem to accelerate HIV disease progression. In this article, we offer guidelines for selecting appropriate candidates for treatment among co-infected inmates.

Comorbidity↗
PubMed1998

Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA.

OBJECTIVE: To provide recommendations for the treatment of acquired immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases, including retinitis, colitis, pneumonitis, and neurologic diseases. PARTICIPANTS: A 17-member panel of physicians with expertise in clinical and virological research and inpatient care in the field of CMV diseases. EVIDENCE: Available clinical and virological study results. Recommendations are rated according to the quality and strength of available evidence. Recommendations were limited to the treatment of CMV diseases; prophylaxis recommendations are not included. PROCESS: The panel was convened in February 1997 and met regularly through November 1997. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although the epidemiological features of CMV diseases are changing in the setting of potent, combination antiretroviral therapy, continued attention must be paid to CMV diseases in patients infected with the human immunodeficiency virus to prevent irreversible endorgan dysfunction. The initial and maintenance treatment of CMV retinitis must be individualized based on the characteristics of the lesions, including location and extent, specific patient factors, and characteristics of available therapies among others. Management of relapse or refractory retinitis must be likewise individualized. Ophthalmologic screening for patients at high risk for retinitis or who have a prior diagnosis of extraretinal disease is recommended. Recommendations for gastrointestinal, pulmonary, and neurologic manifestations are included.

AIDS-Related Opportunistic Infections↗
PubMed1998

Pharmacoeconomic analysis of 3 treatment strategies for cytomegalovirus retinitis in patients with AIDS.

A decision-analytical simulation model was constructed to perform a pharmacoeconomic analysis of the following 3 treatment strategies for previously untreated cytomegalovirus (CMV) retinitis in patients with AIDS: (i) intravenous foscarnet (IVF) for induction and maintenance therapy; (ii) intravenous ganciclovir (IVG) for induction and maintenance therapy; and (iii) intravenous ganciclovir for induction therapy, followed by oral ganciclovir for maintenance therapy (IVG-ORG). Patients who experienced significant adverse effects during, or who failed, initial therapy were switched once to one of the other 2 treatments. The model was used to estimate the direct medical cost (from the perspective of a public payer), survival, and survival adjusted for disutility because of lost vision, for each strategy in the first year following treatment initiation. The expected first-year costs of treatment initiated with IVF, IVG and IVG-ORG were $US47,918, $US38,817 and $US32,036 (1994 values), respectively, while expected first-year survival was 41 weeks, 35 weeks and 35 weeks, respectively. The incremental cost per incremental year of survival using IVF was $US78,000 versus IVG and $US138,000 versus IVG-ORG before adjustment for lost vision, and $US93,000 versus IVG and $US166,000 versus IVG-ORG after adjustment for lost vision. About 23% of the cost of the IVG treatment strategy was attributable to treatment-related adverse events, compared with 14% of the cost of IVF and 16% of the cost of IVG-ORG. Because of the high failure rate with IVG-ORG, initial treatment with IVG-ORG frequently led to switching to another treatment. Only 27% of the costs associated with the IVG-ORG treatment strategy were in fact attributable to the cost of induction and maintenance therapy prior to a switch to alternative treatment. In this analysis, initial treatment with IVG-ORG was the least costly approach for treating CMV retinitis in patients with AIDS. Initial treatment with IVF resulted in slightly longer survival adjusted for vision-related quality of life. New treatments for AIDS may reduce the survival benefit of initial treatment with IVF.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Diarrheal diseases associated with HIV infection.

Diarrhea is a major complication of HIV infection and adversely impacts health care costs, quality of life, and even survival of patients. There is a wide variety of potential causes of diarrhea in HIV-infected patients, and the number of pathogens found continues to increase with time. In addition, there is some controversy concerning the role of some organisms in the pathogenesis of diarrhea and the appropriate diagnostic evaluation of affected patients. This article reviews our current understanding of these pathogens and some of the diagnostic and therapeutic approaches for diarrhea associated with HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1997

Diagnosis and treatment of hepatic disease in patients with HIV.

Liver involvement with opportunistic infections and neoplasms is a well-recognized component of AIDS, affecting most patients. The cause of hepatic disease in these patients may be divided into hepatitis, granulomatous disease, mass lesions, vascular lesions, hepatotoxic drugs, and nonspecific findings. With a rational approach, most patients with AIDS and liver disease can be diagnosed and treated in a cost-effective manner with low morbidity.

AIDS-Related Opportunistic Infections↗
PubMed1997

Treatment of gastrointestinal cytomegalovirus infection with twice-daily foscarnet: a pilot study of safety, efficacy, and pharmacokinetics in patients with AIDS.

Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an open-label study to evaluate the safety, efficacy, and pharmacokinetics of 90 mg of intravenous foscarnet/kg of body weight twice daily accompanied by (pre)hydration of 500 to 750 ml. Efficacy was documented endoscopically, while safety was evaluated clinically by patient reports and physical and laboratory observation. The pharmacokinetics of foscarnet was evaluated after the first dose and following approximately 20 days of therapy. Nine patients (90%) responded histopathologically, nine (90%) responded endoscopically, and nine (90%) responded symptomatically to foscarnet therapy. Adverse events resulted in discontinuance of medication in the case of one patient. The mean maximal concentration was 621 microM following the first dose and 687 microM at steady state (P = 0.11). The apparent elimination rate constant and elimination half-life were not different between dose 1 and steady state. There were no significant changes in foscarnet excretion or renal clearance between dose 1 and steady state. The steady-state volume of distribution was 23.4 liters following the first dose and 19.0 liters at steady state (P < 0.002). Twice-daily foscarnet appeared to be safe and efficacious in the treatment of CMV gastrointestinal disease in this study, resulting in endoscopic or histologic improvement in 9 of the 10 (90%) patients. Minor changes in clearance and volume of distribution noted at steady state compared to single-dose administration are readily explained by study design, known information about foscarnet pharmacokinetics, and changes in body weight and creatinine clearance in the patients.

AIDS-Related Opportunistic Infections↗